Bacterial toxins and heart function: heat-labile Escherichia coli enterotoxin B promotes changes in cardiac function with possible relevance for sudden cardiac death.

Bacterial toxins can cause cardiomyopathy, though it is not its most common cause. Some bacterial toxins can form pores in the membrane of cardiomyocytes, while others can bind to membrane receptors. Enterotoxigenic E. coli can secrete enterotoxins, including heat-resistant (ST) or labile (LT) enterotoxins. LT is an AB5-type toxin that can bind to specific cell receptors and disrupt essential host functions, causing several common conditions, such as certain diarrhea. The pentameric B subunit of LT, without A subunit (LTB), binds specifically to certain plasma membrane ganglioside receptors, found in lipid rafts of cardiomyocytes. Isolated guinea pig hearts and cardiomyocytes were exposed to different concentrations of purified LTB. In isolated hearts, mechanical and electrical alternans and an increment of heart rate variability, with an IC50 of ~0.2 µg/ml LTB, were observed. In isolated cardiomyocytes, LTB promoted significant decreases in the amplitude and the duration of action potentials. Na+ currents were inhibited whereas L-type Ca2+ currents were augmented at their peak and their fast inactivation was promoted. Delayed rectifier K+ currents decreased. Measurements of basal Ca2+ or Ca2+ release events in cells exposed to LTB suggest that LTB impairs Ca2+ homeostasis. Impaired calcium homeostasis is linked to sudden cardiac death. The results are consistent with the recent view that the B subunit is not merely a carrier of the A subunit, having a role explaining sudden cardiac death in children (SIDS) infected with enterotoxigenic E. coli, explaining several epidemiological findings that establish a strong relationship between SIDS and ETEC E. coli. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-023-01100-6.

Nutrigenomics of inward rectifier potassium channels.

Inwardly rectifying potassium (Kir) channels play a key role in maintaining the resting membrane potential and supporting potassium homeostasis. There are many variants of Kir channels, which are usually tetramers in which the main subunit has two trans-membrane helices attached to two N- and C-terminal cytoplasmic tails with a pore-forming loop in between that contains the selectivity filter. These channels have domains that are strongly modulated by molecules present in nutrients found in different diets, such as phosphoinositols, polyamines and Mg2+. These molecules can impact these channels directly or indirectly, either allosterically by modulation of enzymes or via the regulation of channel expression. A particular type of these channels is coupled to cell metabolism and inhibited by ATP (KATP channels, essential for insulin release and for the pathogenesis of metabolic diseases like diabetes mellitus). Genomic changes in Kir channels have a significant impact on metabolism, such as conditioning the nutrients and electrolytes that an individual can take. Thus, the nutrigenomics of ion channels is an important emerging field in which we are attempting to understand how nutrients and diets can affect the activity and expression of ion channels and how genomic changes in such channels may be the basis for pathological conditions that limit nutrition and electrolyte intake. In this contribution we briefly review Kir channels, discuss their nutrigenomics, characterize how different components in the diet affect their function and expression, and suggest how their genomic changes lead to pathological phenotypes that affect diet and electrolyte intake.

Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and -neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases.

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.

Functional consequences of lead and mercury exposomes in the heart.

Lead and mercury are heavy metals that are highly toxic to life forms. There are no known physiological processes that require them, and they do not have a particular threshold concentration to produce biologic damage. They are non-biodegradable, and they slowly accumulate in the environment in a dynamic equilibrium between air, water, soil, food, and living organisms. Their accumulation in the environment has been increasing over time, because they were not banned from use in anthropogenic industrial production. In their +2 cationic state they are powerful oxidizing agents with the ability to interfere significantly with processes that require specific divalent cations. Acute or chronic exposure to lead and mercury can produce multisystemic damage, especially in the developing nervous systems of children and fetuses, resulting in variety of neurological consequences. They can also affect the cardiovascular system and especially the heart, either directly through their action on cardiomyocytes or indirectly through their effects on innervation, humoral responses or blood vessel alterations. For example, heart function modified by these heavy metals are heart rate, contraction, excitability, and rhythm. Some cardiac molecular targets have been identified and characterized. The direct mechanisms of damage of these heavy metals on heart function are discussed. We conclude that exposome to these heavy metals, should be considered as a major relevant risk factor for cardiac diseases.